Early decisions in lymphoid development Min Ye and Thomas Graf

Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York-Bronx, NY 10461, USA.
Current Opinion in Immunology (Impact Factor: 7.48). 05/2007; 19(2):123-8. DOI: 10.1016/j.coi.2007.02.007
Source: PubMed


Recent research suggests that lymphoid progenitors in the bone marrow comprise a heterogeneous cell population. This population first loses megakaryocyte/erythroid, and then granulocyte/macrophage, potential before committing to lymphoid lineages. B and T cells can originate by way of different pathways that appear to be used with varying frequencies in the animal. In the bone marrow, B cell specification and commitment is driven by the concerted action of transcription factors and IL-7 signaling. In the thymus, multipotent progenitors become committed to the T-cell lineage through the action of Notch1. The activated intracellular form of Notch1 suppresses transcription factors that can instruct myeloid cell fates, thereby directly coupling extracellular signaling with changes in transcriptional networks. In conclusion, although a lot is known about B and T cell commitment, more work needs to be done to clarify the earliest steps in lymphoid specification.

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Available from: Thomas Graf, Aug 31, 2015
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    • "During bone marrow B lymphopoiesis, B lymphocyte precursors undergo a strictly controlled process of differentiation, passing from pre–pro B to pro-B and then to pre-B stages, phenotypically characterized as fractions A–D (Hardy et al. 1991). Progressively, several molecules, including cKit, are downregulated while CD43 expression is also modulated on the surface of these cells (Hardy & Hayakawa 2001, Ye & Graf 2007). Subsequently, following the successful rearrangement of the B-cell receptor light chain genes, IgM is expressed on the surface of immature B-cells (Burrows et al. 2002). "
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    ABSTRACT: The effects of hyperthyroidism on B cell physiology are still poorly known. In this study, we evaluated the influence of high circulating levels of T3 on bone marrow, blood and spleen B cell subsets, more specifically on B cell differentiation to plasma cells, in C57BL/6 mice daily injected with T3 for fourteen days. As analyzed by flow cytometry, T3-treated mice exhibited increased frequencies of pre-B and immature B cells and decreased percentage of mature B cells in the bone marrow, accompanied by an increased frequency of blood B cells, splenic newly-formed B cells and total CD19+ B cells. T3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220+ cells correlating with an increased percentage of CD138+ plasma cells was observed in the spleen and bone marrow of T3-treated mice. Using ELIspot assay, an increased number of splenic immunoglobulin-secreting B cells from T3-treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or plus treatment with T3. In conclusion, we provide evidence that high circulating levels of T3 stimulate plasmacytogenesis favoring an increase of plasma cells in the bone marrow, a long-lived plasma cell survival niche. These findings suggest that a possible stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.
    Journal of Endocrinology 12/2013; 220(3). DOI:10.1530/JOE-13-0315 · 3.72 Impact Factor
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    • "Macrophages possess both homeostatic and innate immune defense roles in metazoans, necessitating their continual production from hematopoietic precursors. The development of macrophages from progenitor cells, termed monopoiesis, occurs through the interplay between extracellular growth factors and intracellular transcription factors (Cantor and Orkin, 2002; Friedman, 2002; Ye and Graf, 2007; Zhu and Emerson, 2002). The key growth factors that regulate monopoiesis are colony-stimulating factor-1 (CSF-1) (Fixe and Praloran, 1997; Guilbert and Stanley, 1980; Stanley et al., 1997; Tushinski et al., 1982) and interleukin-34 (IL-34) (Chihara et al., 2010; Lin et al., 2008; Wei et al., 2010), which act through the CSF-1 receptor (CSF-1R) to regulate the survival, proliferation , and development of macrophages and their precursors (Hamilton, 1997; Pixley and Stanley, 2004). "
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    ABSTRACT: The development of macrophages is a highly regulated process requiring coordination amongst transcription factors. The presence/absence, relative levels, antagonism, or synergy of all transcription factors involved is critical to directing lineage cell fate and differentiation. While relative levels of many key myeloid transcription factors have been determined in mammalian macrophage differentiation, a similar set of studies have yet to be conducted in a teleost system. In this study, we report on the mRNA levels of transcription factors (cebpa, cjun, cmyb, egr1, gata1, gata2, gata3, lmo2, mafb, pax5, pu.1 and runx1) in sorted goldfish progenitor cells, monocytes, and macrophages from primary kidney macrophage cultures. The mRNA levels of runx1 and pu.1 were significantly higher, gata3 and pax5 mRNA levels were lower, in monocytes compared to progenitors, and the mRNA levels of cjun, egr1, gata2, gata3, mafb and pax5 were significantly decreased in macrophages compared to progenitor cells. The relative mRNA levels of the interferon regulatory factor family of transcription factors, irf1, irf2, irf5, irf7, irf8 and irf9 in sorted progenitors, monocytes and macrophages were also measured. In contrast to other irf family transcription factors examined, irf8 mRNA levels were increased in monocytes compared to progenitors by greater than three-fold, suggesting that irf8 is important for monopoiesis. Lastly, we show the differential regulation of myeloid transcription factor mRNA levels in sorted progenitor cells from 1, 2, or 3-day old cultures in response to the recombinant goldfish growth factors, rgCSF-1 and rgKITLA.
    Developmental and comparative immunology 06/2013; 41(2). DOI:10.1016/j.dci.2013.05.019 · 2.82 Impact Factor
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    • "B cell development is characterized by the generation of the BCR, which consists of a heavy and a light immunoglobulin chain, IgH and IgL, respectively. The expression of the BCR subunits VpreB, λ5, and mb-1 (Cd79a), and the initiation of D-J rearrangements at the IgH locus defines early B cell commitment [41]. The specification of CLPs in the B cell lineage requires two transcription factors, E2A and EBF1, which have been shown to activate the expression of genes essential for the formation of pro-B cells [42]. "
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    ABSTRACT: B cell development is a multistep process that is tightly regulated at the transcriptional level. In recent years, investigators have shed light on the transcription factor networks involved in all the differentiation steps comprising B lymphopoiesis. The interplay between transcription factors and the epigenetic machinery involved in establishing the correct genomic landscape characteristic of each cellular state is beginning to be dissected. The participation of "epigenetic regulator-transcription factor" complexes is also crucial for directing cells during reprogramming into pluripotency or lineage conversion. In this context, greater knowledge of epigenetic regulation during B cell development, transdifferentiation, and reprogramming will enable us to understand better how epigenetics can control cell lineage commitment and identity. Herein, we review the current knowledge about the epigenetic events that contribute to B cell development and reprogramming.
    Comparative and Functional Genomics 08/2012; 2012(5):564381. DOI:10.1155/2012/564381 · 2.03 Impact Factor
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